Overall Survival with Brentuximab Vedotin in Stage III or IV Hodgkin's Lymphoma

N Engl J Med. 2022 Jul 28;387(4):310-320. doi: 10.1056/NEJMoa2206125. Epub 2022 Jul 13.

Abstract

Background: Five-year follow-up in a trial involving patients with previously untreated stage III or IV classic Hodgkin's lymphoma showed long-term progression-free survival benefits with first-line therapy with brentuximab vedotin, a CD30-directed antibody-drug conjugate, plus doxorubicin, vinblastine, and dacarbazine (A+AVD), as compared with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). A planned interim analysis indicated a potential benefit with regard to overall survival; data from a median of 6 years of follow-up are now available.

Methods: We randomly assigned patients in a 1:1 ratio to receive up to six cycles of A+AVD or ABVD. The primary end point, modified progression-free survival, has been reported previously. The key secondary end point was overall survival in the intention-to-treat population. Safety was also assessed.

Results: A total of 664 patients were assigned to receive A+AVD and 670 to receive ABVD. At a median follow-up of 73.0 months, 39 patients in the A+AVD group and 64 in the ABVD group had died (hazard ratio, 0.59; 95% confidence interval [CI], 0.40 to 0.88; P = 0.009). The 6-year overall survival estimates were 93.9% (95% CI, 91.6 to 95.5) in the A+AVD group and 89.4% (95% CI, 86.6 to 91.7) in the ABVD group. Progression-free survival was longer with A+AVD than with ABVD (hazard ratio for disease progression or death, 0.68; 95% CI, 0.53 to 0.86). Fewer patients in the A+AVD group than in the ABVD group received subsequent therapy, including transplantation, and fewer second cancers were reported with A+AVD (in 23 vs. 32 patients). Primary prophylaxis with granulocyte colony-stimulating factor was recommended after an increased incidence of febrile neutropenia was observed with A+AVD. More patients had peripheral neuropathy with A+AVD than with ABVD, but most patients in the two groups had resolution or amelioration of the event by the last follow-up.

Conclusions: Patients who received A+AVD for the treatment of stage III or IV Hodgkin's lymphoma had a survival advantage over those who received ABVD. (Funded by Takeda Development Center Americas and Seagen; ECHELON-1 ClinicalTrials.gov number, NCT01712490; EudraCT number, 2011-005450-60.).

Publication types

  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Antineoplastic Agents, Immunological* / adverse effects
  • Antineoplastic Agents, Immunological* / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols* / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Bleomycin / administration & dosage
  • Bleomycin / adverse effects
  • Brentuximab Vedotin* / administration & dosage
  • Brentuximab Vedotin* / adverse effects
  • Dacarbazine / administration & dosage
  • Dacarbazine / adverse effects
  • Disease-Free Survival
  • Doxorubicin / administration & dosage
  • Doxorubicin / adverse effects
  • Follow-Up Studies
  • Hodgkin Disease* / drug therapy
  • Hodgkin Disease* / mortality
  • Hodgkin Disease* / pathology
  • Humans
  • Neoplasm Staging
  • Survival Analysis
  • Treatment Outcome
  • Vinblastine / administration & dosage
  • Vinblastine / adverse effects

Substances

  • Antineoplastic Agents, Immunological
  • Bleomycin
  • Vinblastine
  • Dacarbazine
  • Brentuximab Vedotin
  • Doxorubicin

Associated data

  • ClinicalTrials.gov/NCT01712490
  • EudraCT/2011-005450-60